Search

Acute administration of the antidepressant drug desipramine (DMI) in man, increased evening melatonin secretion, which reached peak plasma levels 2-4 h earlier than after placebo administration. The increase at set time points 21.00 h-22.00 h was directly proportional to an individual's integrated night-time secretion of melatonin. We have shown that this stimulation was not an effect of DMI inhibition on the hepatic metabolism of melatonin to 6-sulphatoxy melatonin (aMT6s), indeed aMT6s is in itself a good index of the evening melatonin rise. The stimulation of early evening melatonin by DMI might be exploited as a simple pineal function test. [ABSTRACT FROM AUTHOR]

To clarify a controversy as to whether melatonin secretion is related to body weight, urinary sulphatoxymelatonin (aMT6s) excretion was estimated in 10 patients with anorexia nervosa before and after weight gain, and compared with 10 age-matched controls. There was no change in aMT6s excretion after weight gain, and no significant difference between the patients and control groups at either point. Significant increases in plasma LH, FSH, and estradiol were detected after weight gain in anorexic patients, independent of aMT6s excretion. [ABSTRACT FROM AUTHOR]

Depressed patients were carefully matched in pairs with normal subjects for the variables which are known to influence the secretion of melatonin in humans. In contrast to the previous literature, nocturnal melatonin secretion was not lower in the depressed group than in the normal group, and there was no difference in the timing of secretion; indeed, the trend was for greater melatonin secretion in the depressed group. The results are discussed in relation to previous studies, none of which has been so carefully controlled for the relevant variables. [ABSTRACT FROM AUTHOR]

The article presents a study on the efficiency of neuroendocrine rhythms for patients suffering from the Kleine-Levin Syndrome. This syndrome has been previously described as a periodic somnolence and morbid hunger. It occurs in late adolescent males and seldom in females of the same group. The author also presents a case study of a teenage boy who had suffered no previous episodes of psychiatric or neurological disability and eating disorders. In this context, the researchers used the Oxford ambulatory EEG monitoring system. It has been found that episodes of the syndrome were not caused by a gross dysfunction of the biological clock.

Melatonin and cortisol values in plasma were measured hourly over 24 hours in six depressed patients and six normal volunteers before treatment and after one and three weeks of treatment with desipramine. The normal volunteers were further tested one week after withdrawal of desipramine. The mydriatic effects of tyramine and phenylephrine eye drops were also recorded in the normal volunteers. In neither group of subjects did desipramine treatment reduce melatonin secretion, suggesting that functionally significant down-regulation of beta andrenoceptors was not caused by this treatment. Melatonin secretion was significantly increased after three weeks of treatment in depressed patients. This increase was not found in normal subjects. [ABSTRACT FROM AUTHOR]

The plasma concentrations of melatonin in man, fasting and fed, were determined after ingestion of three different oral preparations. A dose of 2 mg was given as either a gelatine capsule, a solution in corn oil or as a slow-release pill. Gelatine capsules and the corn oil preparation gave reproducibly timed peak plasma concentrations, 30 to 60 min after ingestion regardless of nutritional status, and plasma melatonin remained at or above endogenous night-time levels for 3-4 h with mean elimination half-lives of 0.54 to 0.67 h. The slow-release preparation usefully extended high plasma melatonin concentrations for 5-7 h after ingestion but the timing of peak concentrations was very dependent on nutritional status. These preparations should be of use in the study of timed melatonin administration in man. [ABSTRACT FROM AUTHOR]

Plasma melatonin levels were measured at three-hourly intervals over 24 hours in 11 women with untreated anorexia nervosa, and in nine healthy women of normal weight. The circadian rhythm was unaltered but the nocturnal secretion of melatonin was significantly greater in anorectics. It is possible that this was related to nocturnal hypoglycaemia. [ABSTRACT FROM AUTHOR]

Urinary 6-sulphatoxymelatonin (alpha MT6s) excretion was measured after one day and one, two and three weeks of desipramine treatment in eight depressed patients. There was significant increase in the urinary excretion of alpha MT6s after one week of treatment, and at no time was there any decrease in alpha MT6s excretion. These findings are opposed to the hypothesis that desipramine reduces noradrenergic neurotransmission in the human pineal. In a further five patients whose depression was resistant to desipramine alone, urinary alpha MT6s excretion was measured during treatment with adjunctive L-triiodothyronine (T3). There was no change in alpha MT6s excretion, and thus the previously reported potentiation of the efficacy of tricyclic antidepressants in combination with T3 does not appear to be mediated through an alteration in noradrenergic neurotransmission. [ABSTRACT FROM AUTHOR]

Family Medicine (FM) is a new specialty in Ethiopia. The first seven family physicians graduated in February 2016 from the inaugural residency programme at Addis Ababa University. Cooperation amongst Ethiopian and expatriate decision-makers and physicians was needed to begin the programme. Intentional replacement of expatriates with Ethiopian family physicians has begun. Barriers include lack of understanding of FM and the human and financial resources needed for scaling up the programme. Regular programme review with resident physician involvement has allowed the FM training programme to adapt and fit the Ethiopian context. Further successes will result from ongoing support and advocacy from the Federal Ministry of Health and other Ethiopian, African, and international primary care organisations.

Background: Despite well-documented evidence regarding antipsychotic use in older adults residing in nursing homes (NHs), there is a lack of evidence-based use and quality benchmarks for other psychopharmacological medications (PPMs), including antidepressants, anxiolytics, and sedative-hypnotics., Objective: To estimate the prevalence and patterns of use of PPMs and to measure the quality of PPM use., Methods: Using a 5% random sample of 2007 Medicare claims data linked to the Minimum Data Set 2.0, this cross-sectional study identified a nationally representative sample of 69,832 NH residents with ≥3 months of institutionalization. This study measured 1-year prevalence and quality of PPM use, as assessed by indication, dose, and duration of use defined and operationalized according to the current Centers for Medicare and Medicaid Services Unnecessary Medication Guidance for Surveyors and relevant practice guidelines., Results: Over two-thirds of residents (72.1%, n=50,349) used ≥1 PPM in 2007, with the highest prevalence seen in antidepressants (59.4%), and the lowest in anxiolytics (8.9%). Almost two-thirds (61.0%) of PPM users used ≥2 PPM classes. Compared to other PPM therapeutic classes, antipsychotic users had greatest evidence of guideline adequate use by indication (95.8%) and dose (78.7%). In addition, longer duration of adequate treatment was observed among antipsychotic users (mean = 208 days, standard deviation [SD] = 118) as compared to anxiolytic (mean = 159 days, SD = 118) and sedative-hypnotic users (mean = 183 days, SD = 117)., Conclusions: This study found that PPM use remains highly prevalent among long-stay Medicare NH residents. While antipsychotic use remained high (31.5%), little antipsychotic use was deemed inadequate by indication. However, the 1-year prevalence of use, dose, and duration of use of other PPMs remain high and potentially inadequate. Practitioners and policy-makers should heed both the high use and lower prescribing quality of antidepressants, anxiolytics, and sedative-hypnotics in NH residents., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Retrospective analyses of several trials suggest etomidate may be unsafe for intubation in patients with sepsis. We evaluated the association of etomidate and mortality in a large cohort of septic patients to determine if single-dose etomidate was associated with increased in-hospital mortality., Design and Setting: Retrospective cohort study at the Philips eICU Research Institute ICU clinical database., Interventions: None., Patients: Among 741,036 patients monitored from 2008 through 2010, we identified 2,014 adults intubated in the ICU 4-96 hrs after admission, having clinical criteria consistent with sepsis, severe sepsis, or septic shock. In all, 1,102 patients received etomidate and 912 received other induction agents for intubation., Measurements and Main Results: The primary endpoint was in-hospital mortality, but we also evaluated demographic and clinical factors, severity of illness, ICU mortality, ICU length of stay, hospital length of stay, ventilator days, and vasopressor days. Competing risk Cox proportional hazard regression models were used for primary outcomes. Demographics and illness severity were similar between the groups. Hospital mortality was similar between the groups (37.2% vs. 37.8%, p = 0.77), as were ICU mortality (30.1% vs. 30.2%, p = 0.99), ICU length of stay (8.7 days vs. 8.9 days, p = 0.66), and hospital length of stay (15.2 vs. 14.6 days, p = 0.31). More patients in the etomidate group received steroids before and after intubation (52.9% vs. 44.5%, p < 0.001), but vasopressor use and duration of mechanical ventilation were similar. No regression model showed an independent association of etomidate with mortality, shock, duration of mechanical ventilation, ICU or hospital length of stay, or vasopressor use. A hospital mortality model limited to only patients with septic shock (n = 650) also showed no association of etomidate and hospital mortality., Conclusion: In a mixed-diagnosis group of critically ill patients with sepsis, severe sepsis, and septic shock, single-dose etomidate administration for intubation in the ICU was not associated with higher mortality or other adverse clinical outcomes.

Background: There is little knowledge regarding the prevalence and nature of renal impairment in African populations initiating antiretroviral treatment, nor evidence to inform the most cost effective methods of screening for renal impairment. With the increasing availability of the potentially nephrotixic drug, tenofovir, such information is important for the planning of antiretroviral programmes, Methods: (i) Retrospective review of the prevalence and risk factors for impaired renal function in 2189 individuals initiating antiretroviral treatment in a rural African setting between 2004 and 2007 (ii) A prospective study of 149 consecutive patients initiating antiretrovirals to assess the utility of urine analysis for the detection of impaired renal function. Severe renal and moderately impaired renal function were defined as an estimated GFR of < or = 30 mls/min/1.73 m(2) and 30-60 mls/min/1.73 m(2) respectively. Logistic regression was used to determine odds ratio (OR) of significantly impaired renal function (combining severe and moderate impairment). Co-variates for analysis were age, sex and CD4 count at initiation., Results: (i) There was a low prevalence of severe renal impairment (29/2189, 1.3% 95% C.I. 0.8-1.8) whereas moderate renal impairment was more frequent (287/2189, 13.1% 95% C.I. 11.6-14.5) with many patients having advanced immunosuppression at treatment initiation (median CD4 120 cells/microl). In multivariable logistic regression age over 40 (aOR 4.65, 95% C.I. 3.54-6.1), male gender (aOR 1.89, 95% C.I. 1.39-2.56) and CD4<100 cells/ul (aOR 1.4, 95% C.I. 1.07-1.82) were associated with risk of significant renal impairment (ii) In 149 consecutive patients, urine analysis had poor sensitivity and specificity for detecting impaired renal function., Conclusion: In this rural African setting, significant renal impairment is uncommon in patients initiating antiretrovirals. Urine analysis alone may be inadequate for identification of those with impaired renal function where resources for biochemistry are limited.

101 drug users were interviewed at baseline when 6-weeks abstinent. Eighty-four percent reported having drug-related dreams. More subjects reported drug dreams when abstinent than when using drugs. Ninety percent of subjects were followed-up at 6 months. Higher baseline measures of dream frequency were prospectively related to greater drug use. In the first 7 weeks of follow-up there was a rapid reduction in the number of reports, but half of the sample were still experiencing drug dreams in the sixth month. Drug dream frequency at follow-up was related to "craving" and lack of sleep.

It is not known whether in depressed patients antidepressant treatment increases or reduces monoaminergic neurotransmission. Clinical studies are therefore reviewed that investigate adaptive changes at adrenoceptors in depressed patients treated with desipramine, and the net effect of these changes upon neurotransmission. Although in animals chronic desipramine treatment enhances the responsiveness of alpha 1-adrenoceptors to phenylephrine, no such effect could be demonstrated in patients upon the responsiveness of pupil diameter to phenylephrine. However, in keeping with animal studies, clinical evidence of altered responsiveness of alpha 2-adrenoceptors could be demonstrated after chronic desipramine treatment. The alpha 2-mediated growth hormone response to clonidine was increased after one week's treatment with desipramine and then reduced during the second and third weeks of treatment. No clinical measure of the responsiveness of central beta-adrenoceptors is available. However, the secretion of melatonin is a measure of neurotransmission at noradrenergic terminals in the pineal with alpha 1-, alpha 2- and beta 1-adrenoceptors. In normal volunteers the secretion of melatonin was increased by the noradrenaline uptake inhibitors desipramine and (+)-oxaprotiline; (-)-oxaprotiline had no effect. In depressed patients melatonin secretion was increased after three weeks' treatment with desipramine. These and other clinical studies suggest that antidepressant treatments increase noradrenergic neurotransmission in depressed patients.

Whether or not the pineal gland has a significant physiological role in humans is not known. There has nevertheless been speculation about the potential therapeutic use of melatonin (in view of its hypnotic and possible zeitgeber properties) in conditions such as insomnia and jet lag, and in shift-workers. Our work concerns the effects of melatonin administration in humans and the interactions between melatonin and other circadian variables. Chronic (one month), timed (1700 h), low-dose (2 mg daily) melatonin administration to normal subjects without environmental control consistently increased evening fatigue and slightly modified the 24 h prolactin rhythm without effect on cortisol, growth hormone, luteinizing hormone, thyroxine, testosterone or self-rated mood. In five out of 11 subjects the endogenous melatonin rhythm was advanced by one to three hours. During fractional desynchronization of circadian rhythms by increasing imposed 'day' length (26-29 h, 24 days, 500 lux), 5 mg melatonin per os at lights-out in two subjects resulted in better entrainment of the fatigue rhythm to the zeitgeber than in five out of six control subjects, without major consistent effects on other measured circadian variables. Using a new radioimmunoassay for 6-hydroxymelatonin sulphate (aMT6s), the major melatonin metabolite, we have shown that the urinary aMT6s rhythm is closely correlated to that of melatonin in plasma and is completely suppressed by an acute dose of atenolol (100 mg per os), a peripheral beta-adrenergic antagonist. During fractional desynchronization by increasing imposed 'day' length in one subject and decreasing imposed 'day' length in two subjects, the urinary aMT6s rhythm behaved similarly to that of core temperature. The results suggest that fatigue (or alertness) may be entrained by melatonin, but whether critical performance rhythms can be suitably manipulated remains to be clarified. It is likely that melatonin production is linked to the so-called 'strong' circadian oscillator.